This invention relates to a process for producing medical devices on dipping forms, such as surgical and examination gloves or condoms, for example. More particularly, this invention is directed to such a process which imparts superior antimicrobial properties to such devices without causing toxic reactions to the user.
In processes for producing antimicrobial devices it has been routine to incorporate the antimicrobial agent into the material that forms the device, either by including the antimicrobial agent in the device material prior to fabrication or by treatment of the fabricated and functionally independent devices with an antimicrobial agent. Also, when integrating a cationic antimicrobial agent into an anionic latex there are problems of ionic incompatibility. U.S. Pat. No. 4,675,347 describes a technique to resolve the problem by changing the ionic nature of the latex from anionic to cationic or non-ionic through emulsification of the latex with a cationic or non-ionic surfactant.
The special feature of this invention is that by first partially forming flexible gloves in a procedure wherein an initial dipping takes place for forming a latex glove, for example, and subsequently dipping the already formed latex layer into a second bath or dispersion which contains the antimicrobial material, superior antimicrobial results are obtained from the objects produced by such a procedure. That is, when the gloves or other objects of interest formed here, are stripped from the form, the internal surface has the antimicrobial properties immediately adjacent to the wearer's skin when the gloves are subsequently donned by a surgeon, or clinical staff personnel for examination purposes.
Another special feature of this invention is that a cationic antimicrobial agent can be neutralized by the addition of a nonionic or anionic surfactant to overcome the problem of incompatibility of the cationic antimicrobial agent with the anionic latex during mixing.
Many attempts to solve the problem of infection have been directed toward incorporating into plastic articles such as catheters and vascular grafts an antimicrobial agent. For example, U.S. Pat. No. 3,695,921 discloses a catheter coated with a layer of hydrophilic polymer having an antibiotic absorbed therein. European published Application No. 229,862 teaches thermoplastic polyurethane medical devices having an antimicrobial agent on its surface. In addition, U.S. Pat. No. 4,581,028 teaches infection resistant plastic medical articles, such as vascular grafts, having incorporated antimicrobial agents such as silver sulfadiazine and pipericillin. These articles are prepared by dipping procedures.
In addition, U.S. Pat. No. 4,479,795 discloses medical devices of permeable polymers, including a carboxylate antimicrobial agent, which diffuses to the surface of the device to form an antimicrobial barrier. Japanese Patent Application No. SHO 60-36064 teaches a polyurethane or silicone catheter dipped in an aqueous solution of chlorhexidine to absorb the chlorhexidine into the polymer. PCT Published Application No. W086/02561 teaches a medical device of a hydrophobic thermoplastic polymer having up to one percent chlorhexidine base coated thereon or incorporated therein.
Other publications along this line include U.K. Patent Application No. 2084466A, U.S. Pat. No(s). 4,713,402, 4,521,564 and 4,642,242.
Finally, U.S. Pat. No. 4,678,660 discloses a polyurethane article having coated on the surface thereof a layer of polyurethane alloy containing a dispersed complex of a guaternary salt with either an antithrombogenic agent or an antibiotic agent.
In each case, with the prior art discussed above, the antimicrobial agent is incorporated into the material as opposed to being incorporated into a layer applied to an already formed layer of the article still present on the dipping form.
In considering generally the conditions for carrying out the invention herein, one may note that an antimicrobial glove may be made by coating or treating the glove with a material containing the antimicrobial agents. Bisbiguanides have long been used for this purpose and chlorhexidine is the best known product. It has been used for many years in formulations for hand washes and surgical scrubs. However, the material, as stated above, was applied in the dispersions or other formulations forming the device, or absorbed into the surface. No one has suggested incorporating the antimicrobial agent into a separate dispersion or composition for a separate application to an already partially formed layer of the object in question. Also no one has proposed the use of an anionic latex directly with a modified cationic antimicrobial agent.
For example, a gelled latex glove film in accordance with this invention may be dipped into a polyurethane aqueous dispersion (or solution) or a second latex compound containing P-chloro-m-xylenol, preferably with the dry weight concentration range of within the range of between about five and thirty percent, prior to the normal glove cure process. After curing, the glove is dipped into a lubricant dispersion or solution containing an antimicrobial surfactant such as, for example, Nonidet P-40 which is octylphenoxy-poly(ethoxyethanol) and a chlorhexidine base or its salts such as, for example, acetate, gluconate or hydrochloride, or a combination of these. The preferred range of the chlorhexidine base or its salts and the surfactant is within the range of between about one and fifty percent, and preferably one and ten percent. The glove is then dried and stripped off the glove form.
Alternatively, a gelled latex glove film may be dipped in an aqueous or alcohol lubricant dispersion or solution containing an antimicrobial surfactant such as Nonidet P-40, as discussed above, and a chlorhexidine base or its salts as discussed above. The preferred range of the chlorhexidine base or its salts and the surfactant is within the range of between about one and fifty percent, and preferably one and ten percent. The glove is then dried, cured and stripped off the form.
As a further alternative approach, a regular finished glove may be immersed in an alcohol solution (for example, methanol, ethanol or isopropanol) or an aqueous solution containing an antimicrobial surfactant such as Nonidet P-40, as discussed above, and a chlorhexidine base or its salts. The preferred range of the chlorhexidine base or its salts and the surfactant is within the range of between about one and fifty percent, and preferably one and ten percent.
As further representative of a general procedure for use in the invention here, a non-latex glove such as plasticized polyvinyl chloride is coated with a solvent based solution consisting of flexible polymers such as, for example, soft polyurethane in methylene chloride. After the coating is dried, it is dipped in an alcohol or aqueous solution containing an antimicrobial surfactant such as Nonidet P-40 and chlorhexidine base or its salts. In this case, the preferred range, again, of the chlorhexidine base or its salts and the surfactant is within the range of one and fifty percent and preferably one and ten percent. The glove is then dried in the final step required prior to stripping, and then stripped off the form.
Alternatively, while the fused plasticized PVC glove is still on the form, it can be dipped into dispersion A described in Example I below, preferably with a higher wetting capability.
The invention here is particularly useful in providing elimination of a wide spectrum of microorganisms. organisms. For example, the layer containing P-chloro-m-xylenol provides a means for killing microorganisms when they try to penetrate the inner layer of glove material. The octylphenoxy- poly (ethoxyethanol) has proven effective against HIV virus, while the addition of chlorhexidine provides either a synergistic or additional effect against microorganisms.
It will be appreciated that with the method of the invention here, the laminates produced may be utilized in various configurations for wear, as discussed above, such as, for example, surgeon's gloves, examination gloves and condoms.
As further illustrative of the method of the invention here, one may note the following examples in which materials are prepared in accordance with the invention here and subsequently tested for their antimicrobial properties. It is to be understood, however, that these examples are being presented with the understanding that they are to have no limiting character on the broad disclosure of the invention, as generally set forth herein, and as directed to one skilled in the art.